Cancer Causes & Control

, Volume 7, Issue 6, pp 605–625 | Cite as

Nutrition, hormones, and breast cancer: Is insulin the missing link?

  • Rudulf Kaaks
Review/Hypothesis

Breast cancer incidence rates are high in societies with a Western lifestyle characterized by low levels of physical activity, and by an energy-dense diet rich in total and saturated fat and refined carbohydrates. Epidemiologic studies, so far mostly on postmenopausal women, have shown that breast cancer risk is increased in hyperandrogenic women, with decreased levels of plasma sex-hormone binding globulin, and with increased levels of testosterone and of free estrogens. This paper describes the role of hyperinsulinemia as a physiologic link between nutritional lifestyle factors, obesity, and the development of a hyperandrogenic endocrine profile, and reviews evidence that may or may not support the theory that chronic hyperinsulinemia is an underlying cause of breast cancer. An hypothesis is presented, stipulating that breast cancer risk is increased not only in hyperandrogenic postmenopausal women, but also in premenopausal women with mild hyperandrogenism and normal (ovulatory) menstrual cycles. The author suggests further investigation as to whether there is a positive association between risk of breast cancer before menopause and subclinical forms of the polycystic ovary syndrome (PCOS), and to what extent diet and physical activity during childhood, by modulating the degree of insulin resistance during adolescence, may or may not be determinants of a PCO-like hyperandrogenic endocrine profile persisting into adulthood.

Key words

Breast cancer insulin insulin-like growth factors nutrition obesity polycystic ovary syndrome puberty steroid hormones 

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References

  1. 1.
    Parkin, DM, Pisani, P, Ferlay, J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993: 54: 594–606.Google Scholar
  2. 2.
    Dunn, JE. Breast cancer among American Japanese in the San Francisco Bay area. Natl Cancer Inst Monogr 1977; 47: 157–60.Google Scholar
  3. 3.
    Trichopoulos, D, Yen, S, Brown, J, Cole, P, MacMahon, B. The effect of Westernization on urine estrogens, frequency of ovulation, and breast cancer risk. (A study of ethnic Chinese in the Orient and the USA.) Cancer 1984; 53: 187–92.Google Scholar
  4. 4.
    Kato, I, Tominaga, S, Kuroishi, T. Relationship between westernization of dietary habits and mortality from breast and ovarian cancers in Japan. Gann 1987; 78: 349–57.Google Scholar
  5. 5.
    Bjarnason, O, Day, NE, Snaedal, G, Tulinius, H. The effect of year of birth on the breast cancer age curve in Iceland. Int J Cancer 1974; 13: 689–96.Google Scholar
  6. 6.
    Wakai, K, Suzuki, S, Ohno, Y, Kawamura, T, Tamakoshi, A, Aoki, R. Epidemiology of breast cancer in Japan. Int J Epidemiol 1995; 24: 285–91.Google Scholar
  7. 7.
    Armstrong, B, Doll, R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 1975; 15: 617–31.Google Scholar
  8. 8.
    Hems, G. The contributions of diet and childbearing to breast-cancer rates. Br J Cancer 1978; 37: 974–82.Google Scholar
  9. 9.
    Eveleth, PB, Tanner, JM. Worldwide Variation In Human Growth. Cambridge, UK: Cambridge University Press, 1976.Google Scholar
  10. 10.
    Micozzi, MS. Nutrition, body size, and breast cancer. Yearbook Phys Anthropol 1985; 28: 175–206.Google Scholar
  11. 11.
    Albanes, D, Taylor, P. International differences in body height and weight and their relationship to cancer incidence. Nutr Cancer 1990; 14: 69–77.Google Scholar
  12. 12.
    Tarone, RE, Chu, KC. Implications of birth cohort patterns in interpreting trends in breast cancer rates. JNCI 1992; 84: 1402–10.Google Scholar
  13. 13.
    Frisch, RE, Wyshak, G, Albright, NL, et al. Lower lifetime occurrence of breast cancer and cancers of the reproductive system among former college athletes. Am J Clin Nutr 1987; 45: 328–35.Google Scholar
  14. 14.
    Bernstein, L, Henderson, BE, Hanish, R, Sullivan-Halley, J, Ross, RK. Physical exercise and reduced breast cancer risk in young women. JNCI 1994; 86: 1403–8.Google Scholar
  15. 15.
    Mittendorf, R, Longnecker, MP, Newcomer, PA, et al. Strenuous physical activity in young adulthood and risk of breast cancer (United States). Cancer Causes Control 1995; 6: 347–53.Google Scholar
  16. 16.
    Welsh, cW. Dietary fat, calories, and mammary gland tumorigenesis. In: Jacobs, MM, ed. Exercise, Calories, Fat and Cancer. New York, NY (USA): Plenum Press 1992: 203–22.Google Scholar
  17. 17.
    Kelsey, JL, Gammon, MD, John, EM. Reproductive factors and breast cancer. Epidemiol Rev 1993; 15: 36–47.Google Scholar
  18. 18.
    Hunter, DJ, Willett, WC. Diet, body size, and breast cancer. Epidemiol Rev 1993; 15: 110–32.Google Scholar
  19. 19.
    Folsom, AR, Kaye, SA, Prineas, RJ, Potter, JD, Gapstur, SM, Wallace, RB. Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal women. Am J Epidemiol 1990; 131: 794–803.Google Scholar
  20. 20.
    Bruning, PF, Bonfrèr, JMG, Hart, AAM, et al. Body measurements, estrogen availability and the risk of human breast cancer: a case-control study. Int J Cancer 1992; 51: 14–9.Google Scholar
  21. 21.
    Schapira, DV, Kumar, NB, Lyman, GH, Cox, CE. Abdominal obesity and breast cancer risk. Ann Intern Med 1990; 112: 182–6.Google Scholar
  22. 22.
    Sellers, TA, Kushi, LH, Potter, JD, et al. Effect of family history, body fat distribution and reproductive factors on the risk of postmenopausal breast cancer. N Engl J Med 1992; 326: 1323–9.Google Scholar
  23. 23.
    den Tonkelaar, I, Seidell, JC, Collette, H. Body fat distribution in relation to breast cancer in women participating in the DOM-project. Breast Cancer Res Treat 1995; 34: 55–61.Google Scholar
  24. 24.
    Ursin, G, Longnecker, MP, Haile, RW, Greenland, S. A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology 1995; 6: 137–41.Google Scholar
  25. 25.
    Byers, T. Nutritional risk factors for breast cancer. Cancer 1994; 74: 288–95.Google Scholar
  26. 26.
    Howe, GR, Hirohata, T, Bishop, TG, et al. Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies. JNCI 1990; 82: 561–9.Google Scholar
  27. 27.
    Boyd, NF, Noffel, MM, Lockwood, GA, Tritchler, DL. A meta-analysis of dietary fat and breast cancer risk. Br J Cancer 1993; 68: 627–36.Google Scholar
  28. 28.
    MacKenzie, I. The production of mammary cancer in rats using oestrogens. Br J Cancer 1955; 9: 284–99.Google Scholar
  29. 29.
    Staszewski, J. Age at menarche and breast cancer. JNCI 1971; 47: 935–40.Google Scholar
  30. 30.
    Trichopoulus, D, MacMahon, B, Cole, P. Menopause and breast cancer risk. JNCI 1972; 48: 605–13.Google Scholar
  31. 31.
    Clemmesen, J. Statistical Studies in Malignant Neoplasms. Volume 1. Copenhagen, Denmark: Munksgaard, 1965.Google Scholar
  32. 32.
    Lilienfeld, AM. The relationship of cancer of the female breast to artificial menopause and marital status. Cancer 1956; 9: 927–34.Google Scholar
  33. 33.
    Zumoff, B. Hormonal profiles in women with breast cancer. Anticancer Res 1988; 8: 627–36.Google Scholar
  34. 34.
    Siiteri, PK, Hammond, GL, Nisker, JA. Increased availability of serum estrogens in breast cancer: a new hypothesis. In: Pike, MC, Siiteri, PK, Welsch, CW, eds. Hormones and Breast Cancer. Cold Spring Harbor, NY (USA): Cold Spring Harbor Laboratory, 1981; Banbury Report No. 8: 87–106.Google Scholar
  35. 35.
    Pardridge, WM. Serum availability of sex steroid hormones. Clin Endocrinol Metab 1986; 15: 259–78.Google Scholar
  36. 36.
    Mendel, CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989; 10: 232–74.Google Scholar
  37. 37.
    Key, TJA, Pike, MC. The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 1988; 24: 29–43.Google Scholar
  38. 38.
    Bernstein, L, Ross, RK. Endogenous hormones and breast cancer risk. Epidemiol Rev 1993; 15: 48–65.Google Scholar
  39. 39.
    Toniolo, PG, Levitz, M, Zeleniuch-Jacquotte, A, et al., A prospective study of endogenous estrogens and breast cancer in postmenopausal women. JNCI 1995; 87: 190–7.Google Scholar
  40. 40.
    Dorgan, JF, Longcope, C, Stephenson, HE, et al. Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomark Prev 1996; 5: 533–9.Google Scholar
  41. 41.
    Grattarola, R. Androgens in breast cancer. I. Atypical endometrial hyperplasia and breast cancer in married premenopausal women. Am J Obstet Gynaecol 1973; 116: 324–8.Google Scholar
  42. 42.
    Grattarola, R, Secreto, G, Recchione, C, Castellini, W. Androgens and breast cancer. II. Endometrial adenocarcinoma and breast cancer in married postmenopausal women. Am J Obstet Gynaecol 1974; 118: 173–8.Google Scholar
  43. 43.
    Sommers, SC, Theloh, HA. Ovarian stromal hyperplasia in breast cancer. Arch Pathol 1952; 53: 160–7.Google Scholar
  44. 44.
    Sommers, SC. Endocrine abnormalities in women with breast cancer. Lab Invest 1955; 4: 160–74.Google Scholar
  45. 45.
    Adams, J, Polson, DW, Franks, S. Prevalence of polycystic ovaries in women with anovulation and idiopatic hisutism. Br Med J 1986; 293: 355–9.Google Scholar
  46. 46.
    Conway, GS, Honour, JW, Jacobs, HS. Heterogeneity of the polycystic ovary syndrome: clinical, endocrine, and ultrasound features in 556 patients. Clin Endocrinol 1989; 30: 459–70.Google Scholar
  47. 47.
    Franks, S. Polycystic ovary syndrome: a changing perspective. Clinical Endocrinol 1989; 31: 87–120.Google Scholar
  48. 48.
    Secreto, G, Fariselli, G, Bandieramonte, G, Recchione, C, Dati, V, DiPietro, S. Androgen excretion in women with a family history of breast cancer or with epithelial hyperplasia or cancer of the breast. Eur J Cancer Clin Oncol 1983; 19: 5–10.Google Scholar
  49. 49.
    Secreto, G, Toniolo, P, Berrino, F, et al. Increased androgenic activity and breast cancer risk in premenopausal women. Cancer Res 1984; 44: 5902–5.Google Scholar
  50. 50.
    Secreto, G, Recchione, C, Fariselli, G, DiPietro, S. High testosterone and low progesterone levels in premenopausal patients with hyperplasia and cancer of the breast. Cancer Res 1984; 44: 841–4.Google Scholar
  51. 51.
    Secreto, G, Toniolo, P, Pisani, P, et al. Androgens and breast cancer in premenopausal women. Cancer Res 1989; 49: 471–6.Google Scholar
  52. 52.
    Secreto, G, Recchione, C, Cavalleri, M, Miraglia, M, Dati, V. Circulating levels of testosterone, 17β-oestradiol, luteinizing hormone and prolactin in postmenopausal breast cancer patients. Br J Cancer 1983; 47: 269–75.Google Scholar
  53. 53.
    Secreto, G, Toniolo, P, Berrino, F, et al. Serum and urinary androgens and risk of breast in postmenopausal women. Cancer Res 1991; 51: 2572–6.Google Scholar
  54. 54.
    Malarkey, WB, Schroeder, LL, Stevens, VC, James, AG, Lanese, RR. Twenty-four-hour preoperative endocrine profiles in women with benign and malignant breast disease. Cancer Res 1977; 37: 4655–9.Google Scholar
  55. 55.
    McFadyen, IJ, Forrest, APM, Prescott, RJ, et al. Circulating hormone levels in women with breast cancer. Lancet 1976; i: 1100–2.Google Scholar
  56. 56.
    Adami, HO, Johansson, EDB, Vegelius, J, Victor, A. Serum concentrations of estrone, androstenedione, testosterone and sex-hormone-binding globulin in postmenopausal women with breast cancer and in age-matched controls. Uppsala J Med Sci 1979; 84: 259–74.Google Scholar
  57. 57.
    Hill, P, Garbaczewski, L, Kasumi, F. Plasma testosterone and breast cancer. Eur J Cancer Clin Oncol 1985; 21: 1256–66.Google Scholar
  58. 58.
    Wysowski, DK, Comstock, GW, Helsing, KJ, Lau, HL. Sex hormone levels in serum in relation to the development of breast cancer. Am J Epidemiol 1987; 125: 791–9.Google Scholar
  59. 59.
    Garland, CF, Friedlander, NJ, Barrett-Connor, E, Khaw, KT. Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. Am J Epidemiol 1992; 135: 1220–30.Google Scholar
  60. 60.
    Berrino, F, Muti, P, Micheli, A, et al. Serum sex hormone levels after menopause and subsequent breast cancer. JNCI 1996; 88: 291–6.Google Scholar
  61. 61.
    Evans, D, Hoffmann, RG, Kalkhoff, RK, Kissebah, AH. Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolite aberrations in premenopausal women. J Clin Endocrinol Metab 1983; 57: 304–10.Google Scholar
  62. 62.
    Seidell, JC, Cigolini, M, Deurenberg, P, Oosterlee, A, Doornbos, G. Fat distribution, androgens, and metabolism in nonobese women. Am J Clin Nutr 1989; 50: 269–73.Google Scholar
  63. 63.
    Seidell, JC, Cigolini, M, Charzewska, J, et al. Androgenicity in relation to body fat distribution and metabolism in 38-year old women — the European fat distribution study. J Clin Epidemiol 1990; 43: 21–34.Google Scholar
  64. 64.
    Krotkiewski, M, Seidell, JC, Björntorp, P. Glucose tolerance and hyperinsulinemia in obese women: role of adipose tissue distribution, muscle fiber characteristics and androgens. J Intern Med 1990; 228: 385–92.Google Scholar
  65. 65.
    Weaver, JU, Holly, JMP, Kopelman, PG, et al. Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. Clin Endocrinol 1990; 33: 415–22.Google Scholar
  66. 66.
    Kaye, SA, Folsom, AR, Soler, JT, Prineas, RJ, Potter, JD. Associations of body mass and fat distribution with sex hormone concentrations in postmenopausal women. Int J Epidemiol 1991; 20: 151–6.Google Scholar
  67. 67.
    Peiris, AN, Sothman, MS, Aiman, MS, Kissebah, AH. The relationship of insulin to sex hormone-binding globulin: role of adiposity. Fertil Steril 1989; 52: 69–72Google Scholar
  68. 68.
    Soler, JT, Folsom, AR, Kaye, SA, Prineas, RJ. Associations of abdominal adiposity, fasting insulin, sex hormone binding globulin, and estrone with lipids and lipoproteins in post-menopausal women. Atherosclerosis 1989; 79: 21–7.Google Scholar
  69. 69.
    Haffner, SM, Dunn, JF, Katz, MS. Relationship of sex-hormone-binding globulin to lipid, lipoprotein, glucose, and insulin concentrations in postmenopausal women. Metabolism 1992; 41: 278–84.Google Scholar
  70. 70.
    Preziosi, P, Barrett-Connor, E, Papoz, L, et al. Interrelation between plasma sex hormone-binding globulin and plasma insulin in healthy adult women: the Telecom study. J Clin Endocrinol Metab 1993; 76: 283–7.Google Scholar
  71. 71.
    Anderson, DC. Sex-hormone-binding globulin. Clin Endocrinol 1974; 3: 69–96.Google Scholar
  72. 72.
    Rosner, W. The functions of corticosteroid-binding globulin and sex-hormone-binding globulin: recent advances. Endocr Rev 1990; 11: 80–91.Google Scholar
  73. 73.
    Reaven, GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607.Google Scholar
  74. 74.
    Peiris, AN, Sothman, MS, Hennes, MI, et al. Relative contribution of obesity and body fat distribution to alterations in glucose insulin homeostasis: predictive values of selected indices in premenopausal women. Am J Clin Nutr 1989; 49: 758–64.Google Scholar
  75. 75.
    Kirschner, MA, Samojlik, E, Drejka, M, Szmal, E, Schneider, G, Ertel, N. Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 1990; 70: 473: 9.Google Scholar
  76. 76.
    Kissebah, AH, Vydelingum, N, Murray, et al. Relation of body fat to metabolic complications of obesity. J Clin Endocrinol Metab 1982; 54: 254–60.Google Scholar
  77. 77.
    Evans, DJ, Hoffman, RG, Kalkhoff, RK, Kissebah, AH. Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women. Metabolism 1984; 33: 68–75.Google Scholar
  78. 78.
    Amemiya, T, Kawahara, R, Yoshino, M, Komori, K, Hirata, Y. Population study on the adipose tissue distribution in Japanese women born in 1948. Diabetes Res Clin Prac 1990; 10: S71–6.Google Scholar
  79. 79.
    Evans, DJ, Barth, JH, Burke, CW. Body fat topography in women with androgen excess. Int J Obes 1988; 12: 157–62.Google Scholar
  80. 80.
    Schriock, ED, Buffington, CK, Hubert, GD, et al. Divergent correlations of circulating dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding. J Clin Endocrinol Metab 1988; 66: 1329–31.Google Scholar
  81. 81.
    Buffington, CK, Givens, JR, Kitabchi, AE. Opposing actions of dehydroepiandrosterone and testosterone on insulin sensitivity. Diabetes 1991; 40: 693–700.Google Scholar
  82. 82.
    Poretsky, L. On the paradox of insulin-induced hyperandrogenism in insulin-resistant states. Endocr Rev 1991; 12: 3–13.Google Scholar
  83. 83.
    Kissebah, AH, Peiris, A, Evans, DJ. Mechanisms associating body fat distribution with the abnormal metabolic profile in obesity. Rec Adv Obes Res 1987; 5: 54–9.Google Scholar
  84. 84.
    Leibel, RL, Edens, NK, Fried, SK. Physiologic basis for the control of body fat distribution in humans. Annu Rev Nutr 1989; 9: 417–43.Google Scholar
  85. 85.
    Bouchard, C, Desprès, JP, Mauriège, P. Genetic and non-genetic determinants of regional fat distribution. Endocr Rev 1993; 14: 72–93.Google Scholar
  86. 86.
    Björntorp, P. Insulin resistance and physical exercise in obesity. In: Oomura, Y et al, eds. Progress in Obesity Research. Washington, DC: John Libbey & Company 1990: 259–68.Google Scholar
  87. 87.
    Björntorp, P. Fatty acids, hyperinsulinaemia, and insulin resistance: which comes first? Curr Opin Lipidol 1994; 5: 166–74.Google Scholar
  88. 88.
    Hernandez, ER, Resnick, CE, Holtzclaw, D, Payne, DW, Adashi, EY. Insulin as a regulator of androgen biosynthesis by cultured rat ovarian cells: cellular and pharmacological hormonal actions. Endocrinology 1988; 122: 2034–43.Google Scholar
  89. 89.
    Adashi, EY, Resnick, CE, D'Ercole, AJ, Svoboda, ME, van Wyk, JJ. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocrinol Rev 1985; 6: 400–20.Google Scholar
  90. 90.
    Poretsky, L, Kalin, MF. The gonadotropic function of insulin. Endocrinol Rev 1987; 8: 132–41.Google Scholar
  91. 91.
    Nestler, JE, Strauss, JF. Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocrinol Metab Clin North Am 1991; 20: 807–23.Google Scholar
  92. 92.
    Kiddy, DS, Hamilton-Fairley, D, Seppälä, M, et al. Diet-induced changes in sex hormone binding globulin and free testosterone in women with normal or polycystic ovaries: correlation with serum insulin and insulin-like growth factor-I. Clin Endocrinol 1989; 31: 757–63.Google Scholar
  93. 93.
    von Schoultz, B, Carlström, K. On the regulation of sexhormone-binding globulin — a challenge of an old dogma and outlines of an alternative mechanism. J Steroid Biochem 1989; 2: 327–34.Google Scholar
  94. 94.
    Toscano, V, Balducci, P, Bianchi, P, Mangiantini, A, Sciarra, F. Steroidal and non-steroidal factors in plasma sex hormone binding globulin regulation. J Steroid Biochem Mol Biol 1992; 43: 431–7.Google Scholar
  95. 95.
    Plymate, SR, Matej, LA, Jones, RE, Friedl, KE. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab 1988; 67: 460–4.Google Scholar
  96. 96.
    Plymate, SR, Hoop, RC, Jones, RE, Matej, LA. Regulation of sex hormone-binding globulin production by growth factors. Metabolism 1990; 39: 967–70.Google Scholar
  97. 97.
    Singh, A, Hamilton-Fairley, D, Koistinen, R, et al. Effect of insulin-like growth factor-type I (IGF-I) and insulin on the secretion of sex-hormone binding globulin and IGF-I binding protein (IBP-I) by human hepatoma cells. J Endocrinol 1990; 124: R1–3.Google Scholar
  98. 98.
    Holte, J, Bergh, T, Gennarelli, G, Wide, L. The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women. Clin Endocrinol 1994; 41: 473–81.Google Scholar
  99. 99.
    Rajkhowa, M, Bicknell, J, Jones, M, Clayton, RN. Insulin sensitivity in women with polycystic ovary syndrome: relationship to hyperandrogenemia. Fertil Steril 1994; 61: 605–12.Google Scholar
  100. 100.
    Robinson, S, Kiddy, D, Gelding, SV, et al. The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries. Clin Endocrinol 1993; 39: 351–5.Google Scholar
  101. 101.
    Franks, S, Kiddy, DS, Hamilton-Fairley, D, Bush, A, Sharp, PS, Reed, MJ. The role of nutrition and insulin in the regulation of sex hormone binding globulin. J Steroid Biochem Mol Biol 1991; 39: 835–8.Google Scholar
  102. 102.
    Sharp, PS, Kiddy, DS, Reed, MJ, Anyaoku, V, Johnston, DG, Franks, S. Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome. Clin Endocrinol 1991; 35: 253–7.Google Scholar
  103. 103.
    Van den Brande, JL. Structure of the human insulin-like growth factors: relationship to function. In: Schofield PN. The Insulin-like Growth Factors; Structure and Biological Functions. Oxford, UK: Oxford University Press, 1992: 12–44.Google Scholar
  104. 104.
    Holly, JMP, Wass, JAH. Insulin-like growth factors: autocrine, paracrine or endocrine? New perspectives of the somatomedin hypothesis in the light of recent developments. J Endocrinol 1989; 122: 611–8.Google Scholar
  105. 105.
    Clemmons, DR. Structural and functional analysis of insulin-like growth factors. Br Med Bull 1989; 45: 465–80.Google Scholar
  106. 106.
    Humbel, RE. Insulin-like growth factors I and II. Eur J Biochem 1990; 190: 445–62.Google Scholar
  107. 107.
    Bang, P, Hall, K. Insulin-like growth factors as endocrine and paracrine hormones. In: Schofield PN. The Insulin-like Growth Factors; Structure and Biological Functions. Oxford, UK: Oxford University Press, 1992: 151–77.Google Scholar
  108. 108.
    Moxham, C, Jacobs, S. Insulin-like growth factor receptors. In: Schofield PN. The Insulin-like Growth Factors; Structure and Biological Functions. Oxford, UK: Oxford University Press, 1992: 80–109.Google Scholar
  109. 109.
    Kahn, CR, White, MF. The insulin receptor and molecular mechanisms of insulin action. J Clin Invest 1988; 82: 1151–6.Google Scholar
  110. 110.
    D'Ercole, AJ, Stiles, AD, Underwood, LE. Tissue concentrations of somatomedin C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 1984; 81: 935–9.Google Scholar
  111. 111.
    Cara, JF, Rosenfield, RL. Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology 1988; 123: 733–9.Google Scholar
  112. 112.
    Baxter, RC, Martin, JL. Binding proteins for the insulin-like growth factors: structure, regulation and function. Prog Growth Factor Res 1989; 1: 49–68.Google Scholar
  113. 113.
    Clemmons, DR, Underwood, LE. Nutritional regulation of IGF-I and IGF binding proteins. Annu Rev Nutr 1991; 11: 393–412.Google Scholar
  114. 114.
    Isley, WL, Underwood, LE, Clemmons, DR. Changes in plasma somatomedin-C in response to ingestion of diets with variable protein and energy content. J Parenteral Enteral Nutr 1984; 8: 407–11.Google Scholar
  115. 115.
    Straus, DS. Nutritional regulation of hormones and growth factors that control mammalian growth. FASEB J 1994; 8: 6–12.Google Scholar
  116. 116.
    Clemmons, DR, Klibanski, A, Underwood, LE, et al. Reduction of plasma immunoreactive somatomedin C during fasting in humans. J Clin Endocrinol Metab 1981; 53: 1247–50.Google Scholar
  117. 117.
    Minuto, F, Barreca, A, Adami, GF, et al. Insulin-like growth factor-I in human malnutrition: relationship with some body composition and nutritional parameters. J Parenteral Enteral Nutr 1989; 13: 392–6.Google Scholar
  118. 118.
    Smith, AT, Clemmons, DR, Underwood, LE, Ben-Ezra, V, McMurray, R. The effect of exercise on plasma somatomedin-C/insulin-like growth factor I concentrations. Metabolism 1987; 36: 533–7.Google Scholar
  119. 119.
    Baxter, RC, Cowell, CT. Diurnal rhythm of the growth hormone-independent binding protein for insulin-like growth factors in human plasma. J Clin Endocrinol Metab 1987; 65: 432–40.Google Scholar
  120. 120.
    Conover, CA, Lee, PD, Kanaley, JA, Clarkson, JT, Jensen, MD. Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab 1992; 74: 1355–60.Google Scholar
  121. 121.
    Holly, JM, Biddlecombe, RA, Dunger, DB, et al. Circadian variation of GH-independent IGF-binding protein in diabetes mellitus and its relationship to insulin. A new role for insulin? Clin Endocrinol Oxf 1988; 29: 667–75.Google Scholar
  122. 122.
    Brismar, K, Gutniak, M, Povoa, G, Werner, S, Hall, K. Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus. J Endocrinol Invest 1988; 11: 599–602.Google Scholar
  123. 123.
    Brismar, K, Grill, V, Efendic, S, Hall, K. The insulin-like growth factor binding protein-1 in low and high insulin responders before and during dexamethasone treatment. Metabolism 1991; 40: 728–32.Google Scholar
  124. 124.
    Pekonen, F, Laatikainen, T, Buyalos, R, Rutanen, EM. Decreased 34K insulin-like growth factor binding protein in polycystic ovarian disease. Fertil Steril 1989; 51: 972–5.Google Scholar
  125. 125.
    Holly, JM, Eden, JA, Alaghband-Zadeh, J, et al. Insulin-like growth factor binding proteins in follicular fluid from normal dominant and cohort follicles, polcystic and multicystic ovaries. Clin Endocrinol Oxf 1990; 33: 53–64.Google Scholar
  126. 126.
    Suikkari, AM, Koivisto, VA, Rutanen, EM, Yki-Järvinen, H, Karonen, SL, Seppälä, M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor binding protein. J Clin Endocrinol Metab 1988; 66: 266–72.Google Scholar
  127. 127.
    Cotterill, AM, Cowell, CT, Silink, M. Insulin and variation in glucose levels modify the secretion rates of the growth hormone-independent insulin-like growth factor binding protein-1 in the human hepatoblastoma cell line Hep G2. J Endocrinol 1989; 123: R17–20.Google Scholar
  128. 128.
    Conover, CA, Lee, PD. Insulin regulation of insulin-like growth factor-binding protein production in cultured Hep G2 cells. J Clin Endocrinol Metab 1990; 70: 1062–7.Google Scholar
  129. 129.
    Powell, DR, Suwanichkul, A, Cubbage, ML, DePaolis, LA, Snuggs, MB, Lee, PDK. Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1. J Biol Chem 1991; 266: 18868–76.Google Scholar
  130. 130.
    bar, RS, Boes, M, Clemmons, D, et al. Insulin differentially alters transcapillary movement of intravascular IGFBP-1, IGFBP-2 and endothelial cell IGF-binding proteins in rat heart. Endocrinology 1990; 127: 497–9.Google Scholar
  131. 131.
    Adashi, EY, Resnick, CE, Hurwitz, A, et al. Insulin-like growth factors: the ovarian connection. Hum Reprod 1991; 6: 1213–9.Google Scholar
  132. 132.
    Koistinen, R, Suikkari, AM, Tiitinen, A, Kontula, K, Seppälä, M. Human granulosa cells contain insulin-like growth factor binding protein (IGFBP-1) mRNA. Clin Endocrinol Oxf 1990; 32: 635–40.Google Scholar
  133. 133.
    Yen, SSC. Chronic anovulation caused by peripheral endocrine disorders. In: Yen, SCC, Jaffe, RB, eds. Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. Philadelphia, PA (USA): Saunders Company, 1991: 576–629.Google Scholar
  134. 134.
    Moller, DE, Flier, JS. Insulin resistance-mechanisms, syndromes, and implications. N Engl J Med 1991; 26: 938–48.Google Scholar
  135. 135.
    Dunaif, A. Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Medicine 1995; 98(Suppl 1A): 33S-39S.Google Scholar
  136. 136.
    Zavaroni, I, Bonara, E, Pagliara, M, et al. Risk factors for coronary artery disease in healthy persons with hyper-insulinemia and normal glucose tolerance. N Engl J Med 1989; 320: 702–6.Google Scholar
  137. 137.
    Ferranini, E, Buzzigoli, G, Bonadonna, R, et al. Insulin resistance in essential hypertension. N Engl J Med 1987; 317: 350–7.Google Scholar
  138. 138.
    Beatty, OL, Harper, B, Sheridan, B, Atkinson, AB, Bell, PM, Insulin resistance in offspring of hypertensive parents. Br Med J 1993; 307: 92–6.Google Scholar
  139. 139.
    Allemann, Y, Horber, FF, Colombo, M, et al. Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents. Lancet 1993; 341: 327–31.Google Scholar
  140. 140.
    Hollenbeck, C, Reaven, GM. Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab 1987; 64: 1169–73.Google Scholar
  141. 141.
    Randle, PJ, Garland, PB, Hales, CN, Newsholme, EA. The glucose fatty-acid cycle, its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; i: 785–9.Google Scholar
  142. 142.
    Clark, MG, Rattigan, S, Clark, DG. Obesity with insulin resistance: experimental results. Lancet 1983; ii: 1236–40.Google Scholar
  143. 143.
    DeFronzo, RA. The triumvirate: β-cell, muscle, liver-a collusion responsible for NIDDM. Diabetes 1988; 37: 667–87.Google Scholar
  144. 144.
    O'Dea, K. Westernization, insulin resistance and diabetes in Australian Aborigines. Med J Aust 1991: 155: 258–64.Google Scholar
  145. 145.
    Taylor, SI, Mukherjee, C, Jungas, RL. Studies on the mechanism of activation of adipose tissue pyruvate dehydrogenase by insulin. J Biol Chem 1973; 248: 73–81.Google Scholar
  146. 146.
    Taylor, SI, Mukherjee, C, Jungas, RL. Regulation of pyruvate dehydrogenase in isolated rat liver mitochondria. J Biol Chem 1975; 250: 2028–35.Google Scholar
  147. 147.
    Jeanrenaud, B, Halimi, S, van de Werve, G. Neuro-endocrine disorders seen as triggers of the triad: obesity-insulin resistance-abnormal glucose tolerance. Diabetes Metab Rev 1985; 1: 261–92.Google Scholar
  148. 148.
    Wititsuwannakul, D, Kim, K. Mechanism of palmityl coenzyme A inhibition on liver glycogen synthase. J Biol Chem 1977; 252: 7812–7.Google Scholar
  149. 149.
    Ebeling, P, Koivisto, VA. Non-esterified fatty acids regulate lipid and glucose oxidation and glycogen synthesis in healthy man. Diabetologia 1994; 37: 202–9.Google Scholar
  150. 150.
    Lillioja, S, Mott, DM, Zawadzki, JK, Young, AA, Abbott, WG, Bogardus, C. Glucose storage is a major determinant of in vivo ‘insulin resistance’ in subjects with normal glucose tolerance. J Clin Endocrinol Metab 1986; 62: 922–7.Google Scholar
  151. 151.
    Shulman, GI, Rothman, DL, Jue, T, Stein, P, DeFronzo, RA, Shulman, RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Eng J Med 1990; 322: 223–8.Google Scholar
  152. 152.
    Kraegen, EW, Clark, PW, Jenkins, AB, Dalley, EA, Chilholm, DJ, Storlien, LH. Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes 1991; 40: 1397–403.Google Scholar
  153. 153.
    Kiens, B, Essen-Gustavsson, B, Gad, P, Lithell, H. Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. Clin Physiol 1987; 7: 1–9.Google Scholar
  154. 154.
    Björntorp, P. Metabolic abnormalities in visceral obesity. Ann Med 1992; 24: 3–5.Google Scholar
  155. 155.
    Lonnqvist, F, Thome, A, Nilsell, K, Hoffstedt, J, Arner, P. A pathogenic role of visceral fat beta 3-adrenoreceptors in obesity. J Clin Invest 1995; 95: 1109–16.Google Scholar
  156. 156.
    Mårin, P, Andersson, B, Ottoson, M, et al. The morphology and metabolism of intraabdominal adipose tissue in men. Metabolism 1992; 41: 1242–8.Google Scholar
  157. 157.
    Ferranini, E, Barrett, EJ, Bevilacqua, S. Effect of fatty acids on glucose production and utilization in man. J Clin Invest 1983; 72: 1737–47.Google Scholar
  158. 158.
    Golay, A, Swislocki, ALM, Chen, YDI, Reaven, GM. Relationships between plasma free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and non-insulin-dependent diabetic individuals. Metabolism 1987; 7: 692–6.Google Scholar
  159. 159.
    Williamson, JR, Kreisberg, RA, Felts, PW. Mechanism for the stimulation of gluconeogenesis in perfused rat liver. Proc Natl Acad Sci USA 1966; 56: 247–54.Google Scholar
  160. 160.
    Williamson, JR, Browning, ET, Olson, M. Interrelations between fatty acid oxidation and the control of gluconeogenesis in perfused rat liver. Adv Enzyme Regul 1968; 6: 67–100.Google Scholar
  161. 161.
    Bar, RS, Harrison, LC, Muggeo, M, Gorden, P, Kahn, CR, Roth, J. Regulation of insulin receptors in normal and abnormal physiology in humants. Adv Intern Med 1972; 24: 23–52.Google Scholar
  162. 162.
    Gavin, JR, Roth, J, Neville, DM, de Meyts, P, Buell, DN. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc Natl Acad Sci USA 1974; 7: 84–8.Google Scholar
  163. 163.
    Flier, JS. Insulin receptors and insulin resistance. Annu Rev Med 1983; 34: 145–60.Google Scholar
  164. 164.
    Kahn, CR. Role of insulin receptors in insulin resistant states. Metabolism 1980; 29: 455–66.Google Scholar
  165. 165.
    Fried, SK, Russell, CD, Grauso, NL, Brolin, RE. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J Clin Invest 1993; 92: 2191–8.Google Scholar
  166. 166.
    Ravussin, E, Swinburn, BA. Pathophysiology of obesity. Lancet 1992; 340: 404–8.Google Scholar
  167. 167.
    Wing, RR, Matthews, KA, Kuller, LH, et al. Environmental and familial contributions to insulin levels and change in insulin levels in middle-aged women. JAMA 1992; 268: 1890–5.Google Scholar
  168. 168.
    Ravussin, E, Valencia, ME, Esparza, J, Bennett, PH, Schulz, LO. Effects of a traditional lifestyle on obesity in Pima indians. Diabetes Care 1994; 17: 1067–74.Google Scholar
  169. 169.
    Flatt, JP. Dietary fat, carbohydrate balance, and weight maintenance. In: Klimeš, I, Howard, BV, Storlien, LH, Šebökovà, E, eds. Dietary Lipids and Insulin Action. New York, NY (USA): New York Acad Sci 1993: 122–40.Google Scholar
  170. 170.
    Swinburn, B, Ravussin, E. Energy balance or fat balance? Am J Clin Nutr 1993; 57 (Suppl): 766S-71S.Google Scholar
  171. 171.
    Astrup, A, Raben, A. Obesity: an inherited metabolic deficiency in the control of macronutrient balance? Eur J Clin Nutr 1992; 46: 611–20.Google Scholar
  172. 172.
    Westerterp, KR. Food quotient, respiratory quotient, and energy balance. Am J Clin Nutr 1993; 57(Suppl): 759S-65S.Google Scholar
  173. 173.
    Flatt, JP, Ravussin, E, Acheson, KJ, Jéquier, E. Effects of dietary fat on postprandrial substrate oxidation and on carbohydrate and fat balance. J Clin Invest 1985; 76: 1019–24.Google Scholar
  174. 174.
    Schutz, Y, Flatt, JP, Jéquier, E. Failure of fat to promote fat oxidation: a factor favoring the development of obesity. Am J Clin Nutr 1989; 50: 307–14.Google Scholar
  175. 175.
    Eckel, RH. Insulin resistance: an adaptation for weight maintenance. Lancet 1992; 340: 1452–3.Google Scholar
  176. 176.
    Astrup, A, Buemann, B, Western, P, Toubro, S, Raben, A, Christensen, NJ. Obesity as an adaptation to a high-fat diet: evidence from a cross-sectional study. Am J Clin Nutr 1994; 59: 350–5.Google Scholar
  177. 177.
    Hales, CN, Randle, PJ. Effects of low-carbohydrate diet and diabetes mellitus on plasma concentrations of glucose, non-esterified fatty acid, and insulin during oral glucose-tolerance tests. Lancet 1963; i: 790–4.Google Scholar
  178. 178.
    Fukagawa, NK, Anderson, JW, Hageman, G, Young, VR, Minaker, KL. High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults. Am J Clin Nutr 1990; 52: 524–28.Google Scholar
  179. 179.
    Howard, BV, Abbott, WGH, Swinburn, BA. Evaluation of metabolic effects of substitution of complex carbohydrates for saturated fat in individuals with obesity and NIDDM. Diabetes Care 1991; 14: 786–95.Google Scholar
  180. 180.
    Chen, M, Bergman, RN, Porte, D. Insulin resistance and β-cell dysfunction in aging: the importance of dietary carbohydrate. J Clin Endocrinol Metab 1988; 67: 951–7.Google Scholar
  181. 181.
    Kolterman, OG, Greenfield, M, Reaven, GM, Saekow, M, Olefsky, JM. Effect of a high carbohydrate diet on insulin binding to adipocytes and on insulin action in vivo in man. Diabetes 1979; 28: 731–6.Google Scholar
  182. 182.
    Beck-Nielsen, H, Pedersen, O, Sörensen, NS. Effects of diet on the cellular binding and the insulin sensitivity in young healthy subjects. Diabetologia 1978; 15: 289–96.Google Scholar
  183. 183.
    Grey, N, Kipnis, DM. Effect of diet composition on the hyperinsulinemia of obesity. N Engl J Med 1979: 285: 827–31.Google Scholar
  184. 184.
    Coulston, AM, Liu, GC, Reaven, RM. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Metabolism 1983; 32: 52–6.Google Scholar
  185. 185.
    Danforth, E. Diet and obesity. Am J Clin Nutr 1985; 41: 1132–45.Google Scholar
  186. 186.
    Tucker, LA, Kano, MJ. Dietary fat and body fat: a multivariate study of 205 adult females. Am J Clin Nutr 1992; 56: 616–22.Google Scholar
  187. 187.
    Miller, WC, Lindeman, AK, Wallace, J, Niederpruem, M. Diet composition, energy intake, and exercise in relation to body fat in men and women. Am J Clin Nutr 1990; 52: 426–30.Google Scholar
  188. 188.
    Dreon, DM, Frey-Hewitt, B, Ellsworth, N, Williams, PT, Terry, RB, Wood, PD. Dietary fat: carbohydrate ratio and obesity in middle-aged men. Am J Clin Nutr 1988; 47: 995–1000.Google Scholar
  189. 189.
    Romieu, I, Willett, WC, Stampfer, MJ, et al. Energy intake and other determinants of relative weight. Am J Clin Nutr 1988; 47: 406–12.Google Scholar
  190. 190.
    Lilienthal Heitman, B, Lissner, L, Sörensen, TIA, Bengtsson, C. Dietary fat and weight gain in women genetically predisposed for obesity. Am J Clin Nutr 1995; 61: 1213–7.Google Scholar
  191. 191.
    Gazzaniga, JM, Burns, TL. Relationship between diet composition and body fatness, with adjustment for resting energy expenditure and physical activity, in preadolescent children. Am J Clin Nutr 1993; 58: 21–8.Google Scholar
  192. 192.
    Parker, DR, Weiss, ST, Troisi, R, Cassano, PA, Vokonas, PS, Landsberg, L. Relationship of dietary fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study. Am J Clin Nutr 1993; 58: 129–36.Google Scholar
  193. 193.
    Mayer, EJ, Newman, B, Quesenberry, CP, Selby, JV. Usual dietary fat intake and insulin concentrations in healthy women twins. Diabetes Care 1991; 16: 1459–69.Google Scholar
  194. 194.
    Maron, DJ, Fair, JM, Haskell, WL, et al. Saturated fat intake and insulin resistance in men with coronary heart disease. Circulation 1991; 84: 2020–7.Google Scholar
  195. 195.
    Lovejoy, J, DiGirolamo, M. Habitual dietary intake and insulin sensitivity in lean and obese adults. Am J Clin Nutr 1992; 55: 1174–9.Google Scholar
  196. 196.
    Feskens, EJM, Kromhout, D. Habitual dietary intake and glucose tolerance in euglycaemic men: the Zutphen study. Int J Epidemiol 1990; 19: 953–59.Google Scholar
  197. 197.
    Marshall, JA, Hamman, RF, Baxter, J. High-fat, low-carbohydrate diet and the etiology of non-insulin-dependent diabetes mellitus: the San Luis Valley Diabetes Study. Am J Epidemiol 1991; 134: 590–603.Google Scholar
  198. 198.
    Tsunehara, CH, Leonetti, DL, Fujimoto, WY. Diet of secondgeneration Japanese-American men with and without noninsulin-dependent diabetes. Am J Clin Nutr 1990; 52: 731–8.Google Scholar
  199. 199.
    Field, CJ, Ryan, EA, Thompson, ABR, Clandinin, MT. Diet fat composition alters membrane phospholipid composition, insulin binding, and glucose metabolism in adipocytes from control and diabetic animals. J Biol Chem 1990; 19: 11143–50.Google Scholar
  200. 200.
    Storlien, LH, Kraegen, EW, Chishol, DJ, Ford, GL, Bruce, DG, Pascoe, WS. Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 1987; 237: 885–8.Google Scholar
  201. 201.
    Hainault, I, Carlotti, M, Hajduch, E, Guichard, C, Lavau, M. Fish oil in a high-lard diet prevents obesity, hyperlipemia, and adiposcyte insulin resistance in rats. Ann NY Acad Sci 1993; 683: 98–101.Google Scholar
  202. 202.
    Pelikanova, T, Kohout, M, Valek, J, Base, J, Kazdova, L. Insulin secretion and insulin action related to the serum phospholipid fatty acid pattern in healthy men. Metabolism 1989; 38: 188–92.Google Scholar
  203. 203.
    Borkman, M, Storlien, LH, Pan, DA, Jenkins, AB, Chisholm, DJ, Campbell, LV. The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. N Engl J Med 1993; 328: 238–44.Google Scholar
  204. 204.
    Ruiz-Gutierrez, V, Stifel, P, Villar, J, Garcia-Donas, MA, Acosta, D, Carneado, J. Cell membrane fatty acid composition type 1 (insulin-dependent) diabetic patients: relationship with sodium transport abnormalities and metabolic control. Diabetologia 1993; 36: 850–6.Google Scholar
  205. 205.
    Agostoni, C, Riva, E, Bellu, R, Vicenzo, SS, Grazia, BM, Giovannini, M. Relationships between the fatty acid status and insulinemic indexes in obese children. Prostaglandins Leukot Essent Fatty Acids 1994; 51: 317–21.Google Scholar
  206. 206.
    Feskens, EJM, Loeber, JG, Kromhout, D. Diet and physical activity as determinants of hyperinsulinaemia: the Zutphen elderly study. Am J Epidemiol 1994; 140: 350–60.Google Scholar
  207. 207.
    Trevisan, M, Krogh, V, Freudenheim, J, et al. Consumption of olive oil, butter, and vegetable oils and coronary heart disease risk factors. JAMA 1990; 263: 688–92.Google Scholar
  208. 208.
    Popp-Snijders, C, Schouten, JA, Heine, RJ, van der Meer, J, ven der Veen, EA. Dietary supplementation of omega 3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin dependent diabetes. Diabetes Res 1987; 4: 141–7.Google Scholar
  209. 209.
    Schectman, G, Kaul, S, Kissebah, AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988; 37: 1567–73.Google Scholar
  210. 210.
    Pilch, PF, Thompson, PA, Czech, MP. Coordinate modulation of D-glucose transport activity and bilayer fluidity in plasma membranes derived from control and insulintreated adipocytes. Proc Natl Acad Sci USA 1980; 77: 915–8.Google Scholar
  211. 211.
    Ginsberg BH, Jabour J, Spector AA. Increased membrane fluidity is associated with greater sensitivity to insulin (Abstract). Diabetes 1987; 36(Suppl 1): 51A.Google Scholar
  212. 212.
    Truswell, AS. Glycaemic index of foods. Eur J Clin Nutr 1992; 46(Suppl 2): S91–101.Google Scholar
  213. 213.
    Jenkins, DA, Wolever, TMS, Taylor, RH, et al. Glycemic index of foods: a physiological basis for carbohydrate exchange. Am J Clin Nutr 1981; 34: 362–6.Google Scholar
  214. 214.
    Collings, P, Williams, C, Macdonald, I. Effects of cooking on serum glucose and insulin responses to starch. Br Med J 1981; 282: 1032–3.Google Scholar
  215. 215.
    Brand, JC, Nicholson, PL, Thorburn, AW, Truswell, AS. Food processing and the glycemic index. Am J Clin Nutr 1985; 42: 1192–6.Google Scholar
  216. 216.
    Crapo, PA. Simple versus complex carbohydrate use in the diabetic diet. Annu Rev Nutr 1985; 5: 95–114.Google Scholar
  217. 217.
    Wolever, TMS. The glycemic index. In: Bourne, GH ed. Aspects of Some Vitamins, Minerals and Enzymes in Health and Disease. World Rev Nutr Diet (Basel, Karger) 1990; 62: 120–85.Google Scholar
  218. 218.
    Jenkins, DJA, Wolever, TMS, Jenkins, AL, Lee, R, Wong, GS, et al. Glycemic response to wheat products: reduced response to pasta but no effects of fiber. Diabetes Care 1983; 6: 155–90.Google Scholar
  219. 219.
    O'Dea, K, Nestel, PJ, Antonoff, L. Physical factors influencing postprandrial glucose and insulin responses to starch. Am J Clin Nutr 1980; 33: 760–5.Google Scholar
  220. 220.
    Jenkins, DJA, Wesson, V, Wolever, TMS, et al. Wholemeal versus wholegrain breads: proportion of whole or cracked grain and the glycaemic response. Br Med J 1988; 297: 958–60.Google Scholar
  221. 221.
    Manolio, TA, Savage, PJ, Burke, GL, et al. Correlates of fasting insulin levels in young adults: the CARDIA study. J Clin Epidemiol 1991; 44: 571–8.Google Scholar
  222. 222.
    Feskens, EJ, Kromhout, D. Habitual dietary intake and glucose tolerance in euglycemic men: the Zutphen study. Int J Epidemiol 1990; 19: 953–9.Google Scholar
  223. 223.
    Marshall, JA, Weiss, NS, Hamman, RF. The role of dietary fibre in the etiology of non-insulin-dependent diabetes mellitus. Ann Epidemiol 1993; 3: 18–26.Google Scholar
  224. 224.
    Harlan, LC, Harlan, WR, Landis, JR, Goldstein, NG. Factors associated with glucose tolerance in US adults. Am J Epidemiol 1987; 126: 674–84.Google Scholar
  225. 225.
    Hill, JO, Prentice, AM. Sugar and body weight regulation. Am J Clin Nutr 1995; 62(Suppl): 264S-74S.Google Scholar
  226. 226.
    Koivisto, VA, Yki-Jarvinen, H, DeFronzo, RA. Physical training and insulin sensitivity. Diabetes Metab Rev 1988; 1: 445–81.Google Scholar
  227. 227.
    Regensteiner, JG, Mayer, EJ, Shetterly, SM, et al. Relationship between habitual physical activity and insulin levels among nondiabetic men and women. Diabetes Care 1991; 14: 1066–74.Google Scholar
  228. 228.
    Dowse, GK, Zimmet, PZ, Gareeboo, H, et al. Abdominal obesity and physical inactivity are risk factors for NIDDM and impaired glucose tolerance in Indian, Creole, and Chinese Mauritians. Diabetes Care 1991; 14: 271–82.Google Scholar
  229. 229.
    Lindgarde, F, Saltin, B, Daily physical activity, work capacity and glucose tolerance in lean and obese normo-glycaemic middle-aged men. Diabetologia 1981; 20: 137–8.Google Scholar
  230. 230.
    Wang, JT, Ho, LT, Tang, KT, Wang, LM, Chen, YDI, Reaven, GM. Effect of habitual physical activity on age-related glucose intolerance. J Am Geriatr Soc 1989; 37: 203–9.Google Scholar
  231. 231.
    Manson, JE, Rimm, E, Stampfer, MJ, et al. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet 1991; 338: 774–8.Google Scholar
  232. 232.
    Holly, JMP, Smith, CP, Dunger, DB, et al. Relationship between the pubertal fall in sex hormone binding globulin and insulin-like growth factor binding protein-I. A synchronized approach to pubertal development? Clin Endocrinol 1989; 31: 277–84.Google Scholar
  233. 233.
    Belgorosky, A, Rivarola, MA. Progressive increase in nonsex hormone-binding-globulin-bound testosterone and estradiol from infancy to late puberty in girls. J Clin Endocrinol Metab 1988; 67: 234–7.Google Scholar
  234. 234.
    Bartsch, W, Horst, HJ, Derwahl, KM. Interrelations between sex-hormone-binding globulin and 17β-estradiol, testosterone, 5(-dihydroxytestosterone, thyroxine, and triiodothyronine in prepubertal and pubertal girls. J Clin Endocrinol Metab 1980; 50: 1053–6.Google Scholar
  235. 235.
    Apter, D, Vihko, R. Endocrine determinants of fertility: serum androgen concentrations during follow-up of adolescents into the third decade of life. J Clin Endocrinol Metab 1984; 71: 970–4.Google Scholar
  236. 236.
    Apter, D, Bolton, NJ, Hammond, GL, Vihko, R. Serum sex hormone binding globulin during puberty in girls and in different types of adolescent menstrual cycles. Acta Endocrinologica 1984; 107: 413–9.Google Scholar
  237. 237.
    Lee, IR, Lawder, LE, Townend, DC, Wetherall, JD, Hahnel, R. Plasma sex hormone binding globulin concentrations and binding capacity in children before and during puberty. Acta Endocrinologica 1985; 109: 276–80.Google Scholar
  238. 238.
    Holly, JMP, Smith, CP, Dunger, DB, et al. Levels of the small insulin-like growth factor-binding protein are strongly related to those of insulin in prepubertal and pubertal children but only weakly so after puberty. J Endocrinol 1989; 121: 383–7.Google Scholar
  239. 239.
    Argente, J, Barrios, V, Pozo, J, et al. Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age- and sex-related changes. J Clin Endocrinol Metab 1993; 77: 1522–8.Google Scholar
  240. 240.
    Lautala, P, Åkerblom, HK, Viikari, J, et al. Atherosclerosis precursors in Finnish children and adolescents. VII. Serum immunoreactive insulin. Acta Paediatr Scand 1985; 318(Suppl): 127–33.Google Scholar
  241. 241.
    Amiel, SA, Sherwin, RS, Simonson, DC, Lauritano, AA, Tamborlane, WV. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 1986; 315: 215–9.Google Scholar
  242. 242.
    Bloch, CA, Clemons, P, Sperling, MA. Puberty decreases insulin sensitivity. J Pediatr 1987; 110: 481–7.Google Scholar
  243. 243.
    Caprio, S, Plewe, G, Diamond, MD, et al. Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr 1989; 114: 963–7.Google Scholar
  244. 244.
    Smith, CP, Archibald, HR, Thomas, JM, et al. Basal and stimulated insulin levels rise with advancing puberty. Clin Endocrinol 1988; 28: 7–14.Google Scholar
  245. 245.
    Laron, Z, Aurbach-Klipper, Y, Flasterstein, B, Litwin, A, Dickerman, Z, Heding, LG. Changes in endogenous insulin secretion during childhood as expressed by plasma and urinary C-peptide. Clin Endocrinol 1988; 29: 625–32.Google Scholar
  246. 246.
    Travers, SH, Jeffers, BW, Bloch, CA, Hill, JO, Eckel, RH. Gender and Tanner stage differences in body composition and insulin sensitivity in early pubertal children. J Clin Endocrinol Metab 1995; 80: 172–8.Google Scholar
  247. 247.
    Clemmons, DR, van Wyk, JJ. Factors controlling blood concentration of somatomedin C. Clin Endocrinol Metab 1984; 13: 113–43.Google Scholar
  248. 248.
    Smith, CP, Dunger, DB, Williams, AJK, et al. Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life. J Clin Endocrinol Metab 1989; 68: 932–7.Google Scholar
  249. 249.
    Hesse, V, Jahreis, G, Schmabach, H, et al. Insulin-like growth factor I correlations to changes of the hormonal status in puberty and age. Exp Clin Endocrinol 1994; 102: 289–8.Google Scholar
  250. 250.
    Wilson, DW, Killen, JD, Hammer, LD, et al. Insulin-like growth factor-I as a reflection of body composition, nutrition, and puberty in sixth and seventh grade girls. J Clin Endocrinol Metab 1991; 73: 907–12.Google Scholar
  251. 251.
    Copeland, KC, Colletti, RB, Devlin, JT, McAuliffe, TL. The relationship between insulin-like growth factor I, adiposity, and aging. Metabolism 1990; 39: 584–7.Google Scholar
  252. 252.
    Hindmarsh, P, Di Silvio, PJ, Pringle, PJ, Kurtz, AB, Brook, CGD. Changes in serum insulin concentration during puberty and their relationship to growth hormone. Clin Endocrinol 1988; 28: 381–8.Google Scholar
  253. 253.
    Arslanian, SA, Kalhan, SC. Correlations between fatty acid and glucose metabolism: potential explanation of insulin resitance during puberty. Diabetes 1994; 43: 908–14.Google Scholar
  254. 254.
    Benassi, L, Tridenti, G, Orlandi, N, Pezzarossa, A. Glucose tolerance and insulin release in adolescent female. J Endocrinol Invest 1991; 14: 751–6.Google Scholar
  255. 255.
    Rosenfeld, RG, Wilson, DM, Dollar, LA, Bennett, A, Hintz, RL. Both pituitary growth hormone and recombinant DNA-derived growth hormone cause insulin resistance at a postreceptor site. J Clin Endocrinol Metab 1992; 54: 1033–8.Google Scholar
  256. 256.
    Press, M, Tamborlane, WV, Sherwin, RS. Importance of raised growth hormone levels in mediating the metabolic derangements of diabetes. N Engl J Med 1984; 310: 810–5.Google Scholar
  257. 257.
    Rizza, RA, Mandarino, LJ, Gerich, JE. Effects of growth hormone on insulin action in man: Mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes 1982; 31: 663–9.Google Scholar
  258. 258.
    Martha, PM, Reiter, EO. Pubertal growth and growth hormone secretion. Endocrinol Metab Clin North Am 1991; 20: 165–82.Google Scholar
  259. 259.
    Bratusch-Marrain, PR, Smith, D, DeFronzo, RA. The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 1982; 55: 973–82.Google Scholar
  260. 260.
    Zwiauer, KF, Pakosta, R, Mueller, T, Widhalm, K. Cardiovascular risk factors in obese children in relation to weight and body fat distribution. J Am Coll Nutr 1992; 11(Suppl): 41S-50S.Google Scholar
  261. 261.
    Kikuchi, DA, Srinivasan, SR, Harsha, DW, Webber, LS, Sellers, TA, Berenson, GS. Relation of serum lipoprotein lipids and apolipoproteins to obesity in children: the Bogalusa Heart Study. Prev Med 1992; 21: 177–90.Google Scholar
  262. 262.
    Hoffman, RP, Stumbo, PJ, Janz, KF, Nielsen, DH. Altered insulin resistance is associated with increased dietary weight loss in obese children. Horm Res 1995;44: 17–22.Google Scholar
  263. 263.
    Wabitsch, M, Hauner, H, Heinze, E, et al. Body fat distribution and changes in the atherogenic risk-factor profile in obese adolescent girls during weight reduction. Am J Clin Nutr 1994; 60: 54–60.Google Scholar
  264. 264.
    Arslanian, S, Suprasongsin, C. Insulin sensitivity, lipids, and body composition in childhood: is ‘syndrome X’ present? J Clin Endocrinol Metab 1996; 81: 1058–62.Google Scholar
  265. 265.
    Klesges, RC, Klesges, LM, Eck, LH, Shelton, ML. A longitudinal analysis of accelerated weight gain in preschool children. Pediatrics 1995; 95: 126–30.Google Scholar
  266. 266.
    Esposito del Puente, A, Scalfi, L, de Filippo, E, et al. Familial and environmental influences on body composition and body fat distribution in childhood in southern Italy. Int J Obes Relat Metab Disord 1994; 18: 596–601.Google Scholar
  267. 267.
    Pasquali, R, Casimirri, F, Venturoli, S, et al. Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome. Metabolism 1994; 43: 706–13.Google Scholar
  268. 268.
    Rebuffe-Scrive, M, Cullberg, G, Lundberg, PA, Lindstedt, G, Bjorntorp, P. Anthropometric variables and metabolism in polycystic ovarian disease. Horm Metab Res 1989; 21: 391–7.Google Scholar
  269. 269.
    Bringer, J, Lefebvre, P, Boulet, F, et al. Body composition and regional fat distribution in polycystic ovarian syndrome. Relationship to hormonal and metabolic profiles. Ann N Y Acad Sci 1993; 687: 115–23.Google Scholar
  270. 270.
    Lanzone, A, Fulghese, AM, Pappalardo, S, et al. Growth hormone and somatomedin-C secretion in patients with polycystic ovarian disease. Gynecol Obstet Invest 1990; 29: 149–53.Google Scholar
  271. 271.
    Chang, RJ, Nakamura, RM, Judd, HL, Kaplan, SO. J Clin Endocrinol Metab 1983; 57: 356–9.Google Scholar
  272. 272.
    Rittmaster, RS, Deshwal, N, Lehman, L. The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome. J Clin Endocrinol Metab 1993; 76: 1295–1300.Google Scholar
  273. 273.
    Conway, GS, Jacobs, HS, Holly, JMP, Wass, JAS. Effects of luteinizing hormone, insulin, insulin-like growth factor I and insulin-like growth factor small binding protein in the polycystic ovary syndrome. Clin Endocrinol 1990; 33: 593–603.Google Scholar
  274. 274.
    Tropeano, G, Licisano, A, Liberale, I, et al. Insulin, C-peptide, androgens, and beta-endorphin response to oral glucose in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 1994; 78: 305–9.Google Scholar
  275. 275.
    Dunaif, A, Graf, M, Mandeli, J, Laumas, V, Dobrjanski, A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab 1987; 65: 499–507.Google Scholar
  276. 276.
    Dunaif, A, Segal, KR, Futterweit, W, Dobrjansky, A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38: 1165–74.Google Scholar
  277. 277.
    Suikkari, AM, Ruutiainen, K, Erkkola, R, Seppälä, M. Low levels of low molecular weight insulin-like growth factor binding protein in patients with polycystic ovarian disease. Hum Reprod 1989; 4: 136–9.Google Scholar
  278. 278.
    Franks, S, Kiddy, D, Sharp, P, et al. Obesity and polycystic ovary syndrome. Ann NY Acad Sci 1991; 626: 201–6.Google Scholar
  279. 279.
    Kiddy, DS, Hamilton-Fairley, D, Bush, A, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol 1992; 36: 105–11.Google Scholar
  280. 280.
    Venturoli, S, Porcu, E, Fabbri, R, et al. Menstrual irregularities in adolescents: hormonal pattern and ovarian morphology. Hormone Res 1986; 24: 269–79.Google Scholar
  281. 281.
    Polson, DW, Wadsworth, J, Adams, J, Franks, S. Polycystic ovaries — a common finding in normal women. Lancet 1988; i: 870–2.Google Scholar
  282. 282.
    Clayton, RN, Ogden, V, Hodgkinson, J, et al. How common are polycystic ovaries in normal women and what is their significance for the fertility of the population? Clin Endocrinol 1992; 37: 127–34.Google Scholar
  283. 283.
    Abdel-Gadir, A, Khatim, MS, Mowafi, RS, Alnaser, HM, Muharib, NS, Shaw, RW. Implications of ultrasonically diagnosed polycystic ovaries. I. Correlations with basal hormonal profiles. Hum Reprod 1992; 7: 453–7.Google Scholar
  284. 284.
    Nobels, F, Dewailly, D. Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis. Fertil Steril 1992; 58: 655–66.Google Scholar
  285. 285.
    Lucky, AW, Rosenfield, RL, McGuire, J, Rudy, S, Helke, J. Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: Adreanl enzyme defects and exaggerated adrenarche. J Clin Endocrinol Metab 1986; 62: 840–8.Google Scholar
  286. 286.
    Ehrmann, DA, Barnes, RB, Rosenfield, RL. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr Rev 1995; 16: 322–53.Google Scholar
  287. 287.
    Pasquali, R, Casimirri, F. Insulin and androgen relationships with abdominal body fat distribution in women with and without hyperandrogenism. Horm Res 1993; 39: 179–87.Google Scholar
  288. 288.
    Barbieri, RL, Smith, S, Ryan, KJ. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril 1988; 50: 197–212.Google Scholar
  289. 289.
    Rosenfield, RL, Barnes, RB, Cara, JF, Lucky, AW. Dysregulation of cytochrome P450c17 (as the cause of polycystic ovarian syndrome. Fertil Steril 1990; 53: 785–91.Google Scholar
  290. 290.
    Magoffin, DA, Kurtz, KM, Erickson, GF. Insulin-like growth factor selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells. Mol Endocrinol 1990; 4: 489–96.Google Scholar
  291. 291.
    Magoffin, DA, Weitsman, SR. Differentiation of ovarian theca-interstitial cells in vitro: regulation of 17 alpha-hydroxylase messenger ribonucleic acid expression by luteinizing hormone and insulin-like growth factor-I. Endocrinology 1993; 132: 1945–51.Google Scholar
  292. 292.
    Hiney, JK, Ojeda, SR, Dees, WL. Insulin-like growth factor I: a possible metabolic signal involved in the regulation of female puberty. Neuroendocrinology 1991; 54: 420–3.Google Scholar
  293. 293.
    Kazer, R. The etiology of polycystic ovary syndrome (PCO). Med Hypotheses 1992; 30: 151–5.Google Scholar
  294. 294.
    Venturoli, S, Porcu, E, Fabbri, R, et al. Postmenarcheal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities. Fertil Steril 1987; 48: 78–85.Google Scholar
  295. 295.
    Apter, D, Vihko, R. Endocrine determinants of fertility: serum androgen concentrations during follow-up of adolescents into the third decade of life. J Endocrinol Metab 1990; 71: 970–4.Google Scholar
  296. 296.
    Simpson, JL. Elucidating the genetics of polycystic ovary syndrome. In: Dunaif, A, Givens, JR, Haseltine, FP, Merriam, GR, eds. Polycystic Ovary Syndrome. Oxford, UK: Black-well Scientific Publications, 1992: Chapter 6: 59–69.Google Scholar
  297. 297.
    Carey, AH, Chan, KL, Short, F, White, D, Williams, R, Franks, S. Evidence for a single gene effect causing polycystic ovary syndrome and male pattern baldness. Clin Endocrinol 1992; 38: 653–8.Google Scholar
  298. 298.
    Carey, AH, Waterworth, D, Patel, K, et al. Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum Mol Genet 1994; 3: 1873–6.Google Scholar
  299. 299.
    Dunaif, A. Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Med 1995; 98: 1A-33S.Google Scholar
  300. 300.
    Prelevic, GM, Wurzburger, MI, Balint-Peric, I, Ginsburg, J. Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries. Horm Res 1992; 37: 125–31.Google Scholar
  301. 301.
    Kazer, RR, Unterman, TG, Glick, RP. An abnormality of the growth hormone/insulin-like growth factor axis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1990; 71: 958–62.Google Scholar
  302. 302.
    Insler, V, Shoham, Z, Barash, A, et al. Polycystic ovaries in non-obese and obese patients: possible pathophysiological mechanism based on new interpretation of facts and findings. Hum Reprod 1993; 8: 379–84.Google Scholar
  303. 303.
    Insler, V, Barash, A, Shoham, Z, et al. Overnight secretion pattern of growth hormone, sex hormone-binding globulin, insulin-like growth factor I, and its binding protein in obese and non-obese women with polycystic ovarian disease. Isr J Med Sci 1994; 30: 42–7.Google Scholar
  304. 304.
    Kopelman, PG, White, N, Pilkington, TR, Jeffcoate, SL. The effect of weight loss on sex steroid secretion and binding in massively obese women. Clin Endocrinol Oxf 1981; 15: 113–6.Google Scholar
  305. 305.
    Bates, GW, Whitworth, NS. Effect of body weight reduction on plasma androgens in obese, infertile women. Fertil Steril 1982; 38: 406–9.Google Scholar
  306. 306.
    Harlass, FE, Plymate, SR, Fariss, BL, Belts, RP. Weight loss is associated with correction of gonadotropin and sex steroid abnormalities in the obese anovulatory female. Fertil Steril 1984; 42: 649–52.Google Scholar
  307. 307.
    Crave, JC, Fimbel, S, Lejeune, H, Cugnardey, N, Dechaud, H, Pugeat, M. Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab 1995; 80: 2057–62.Google Scholar
  308. 308.
    Wabitsch, M, Hauner, H, Heinze, E, et al. Body fat distribution and steroid hormone concentrations in obese adolescent girls before and after weight reduction. J Clin Endocrinol Metab 1995; 80: 3469–75.Google Scholar
  309. 309.
    Cross, M, Dexter, TM. Growth factors in development, transformation, and tumorigenesis. Cell 1991; 64: 271–80.Google Scholar
  310. 310.
    Baserga, R, Porcu, P, Sell, C. Oncogenes, growth factors and control of the cell cycle. Cancer Surv 1993; 16: 201–13.Google Scholar
  311. 311.
    King, RJB. A discussion of the roles of oestrogen and progestin in human mammary carcinogenesis. J Steroid Biochem Molec Biol 1991; 39: 811–8.Google Scholar
  312. 312.
    Shi, YE, Liu, YE, Lippman, ME, Dickson, RB. Progestins and antiprogestins in mammary tumour growth and metastasis. Hum Reprod 1994; 9: 162–73.Google Scholar
  313. 313.
    Henderson, BE, Ross, R, Bernstein, L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation Award lecture. Cancer Res 1988; 48: 246–53.Google Scholar
  314. 314.
    Fernig, DG, Smith, JA, Rudland, PS. Relationship of growth factors and differentiation and neoplastic development of the mammary gland. In: Lippman, M, Dickson, R, eds. Regulatory Mechanisms in Breast Cancer. Boston, MA (USA): Kluwer Publishers, 1991: 47–78.Google Scholar
  315. 315.
    Henderson, BE, Ross, RK, Judd, HL, Krailo, MD, Pike, MC. Do regular ovulatory cycles increase breast cancer risk? Cancer 1985; 56: 1206–8.Google Scholar
  316. 316.
    Spicer, DV, Pike, MC. The prevention of breast cancer through reduced ovarian steroid exposure. Acta Oncologica 1992; 31: 167–74.Google Scholar
  317. 317.
    Pike, MC, Spicer, DV, Dahmoush, L, Press, MF. Estrogens, progestagens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 1993; 15: 17–35.Google Scholar
  318. 318.
    Key, TJA, Pike, MC. The dose-effect relationship between ‘unopposed’ estrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer 1988; 57: 205–12.Google Scholar
  319. 319.
    Macaulay, VM. Insulin-like growth factors and cancer. Br J Cancer 1992; 65: 311–20.Google Scholar
  320. 320.
    Yee, D, Rosen, N, Favoni, RE, Cullen, KJ. The insulin-like growth factors, their receptors, and their binding proteins in human breast cancer. In: Lippman, Dickson, eds. Regulatory Mechanisms in Breast Cancer. Boston, MA (USA): Kluwer Publishers 1991: 93–105.Google Scholar
  321. 321.
    Hilf, R. The actions of insulin as a hormonal factor in breast cancer. In: Pike, MC, Siiteri, PK, Welsch, CW, eds. Hormones and Breast Cancer. Cold Spring Harbor, NY (USA): Cold Spring Harbor Laboratory, 1981; Banbury Report No. 8: 317–37.Google Scholar
  322. 322.
    Stoll, BA. Breast cancer: the obesity connection. Br J Cancer 1994; 69: 799–801.Google Scholar
  323. 323.
    Bruning, PF, Bonfrèr, JMG, van Noord, PAH, Hart, AAM, de Jong-Bakker, M, Nooijen, WJ. Insulin resistance and breast cancer risk. Int J Cancer 1992; 52: 511–6.Google Scholar
  324. 324.
    Adami, HO, Rimsten, A. Prevalence of hypertension and diabetes in breast cancer: a case-control study in 179 patients and age-matched, non-hospitalized controls. Clin Oncol 1978; 4: 243–9.Google Scholar
  325. 325.
    Ragozzino, M, Melton, LJ, Chu, CP, Palumbo, PJ. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chron Dis 1982; 35: 13–9.Google Scholar
  326. 326.
    O'Mara, BA, Byers, T, Schoenfeld, E. Diabetes mellitus and cancer risk: a multi-site case-control study. J Chron Dis 1985; 38: 435–41.Google Scholar
  327. 327.
    Franceschi, S, la Vecchia, C, Negri, E, Parazzini, F, Boyle, P. Breast cancer risk and history of selected medical conditions linked with female hormones. Eur J Cancer 1990; 26: 781–5.Google Scholar
  328. 328.
    Adami, HO, McLaughlin, J, Ekbom, A, et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control 1991; 2: 307–14.Google Scholar
  329. 329.
    Moseson, M, Koenig, KL, Shore, RE, Pasternack, BS. The influence of medical conditions associated with hormones on the risk of breast cancer. Int J Epidemiol 1993; 22: 1000–9.Google Scholar
  330. 330.
    La Vecchia, C, Negri, E, Franceschi, S, D'Avanzo, B, Boyle, P. A case-control study of diabetes mellitus and cancer risk. Br J Cancer 1994; 70: 950–3.Google Scholar
  331. 331.
    Andersson, B, Marin, P, Lissner, L, Vermeulen, A, Bjorntorp, P. Testosterone concentrations in women and men with NIDDM. Diabetes Care 1994; 17: 405–11.Google Scholar
  332. 332.
    Nyholm, H, Djursing, H, Hagen, C, Agner, T, Bennett, P, Svenstrup, B. Androgens and estrogens in postmenopausal insulin-treated diabetic women. J Clin Endocrinol Metab 1989; 69: 946–9.Google Scholar
  333. 333.
    Djursing, H, Hagen, C, Nyboe-Andersen, A, Sventrup, B, Bennet, P, Mølsted-Pedersen, L. Serum sex hormone concentrations in insulin dependent diabetic women with and without amenorrhea. Clin Endocrinol 1985; 23: 147–54.Google Scholar
  334. 334.
    Prelevic, GM, Wurzburger, MI, Peric, LA. The effect of residual beta-cell activity on menstruation and the reproductive hormone profile of insulin-dependent diabetics. Arch Gynecol Obstet 1989; 244: 207–13.Google Scholar
  335. 335.
    Alexander, L, Appleton, D, Hall, R, Ross, WM, Wlikinson, R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol Oxf 1980; 12: 71–9.Google Scholar
  336. 336.
    Nabarro, JDN. Acromegaly. Clin Endocrinol Oxf 1987; 26: 481–512.Google Scholar
  337. 337.
    Bengtsson, BÅ, Edén, S, Ernest, I, Odén, A, Sjögren, B. Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 1988; 223: 327–35.Google Scholar
  338. 338.
    Ron, E, Gridley, G, Hrubec, Z, Page, W, Arora, S, Fraumeni, JFJr. Acromegaly and gastrointestinal cancer. Cancer 1991; 68: 1673–7.Google Scholar
  339. 339.
    Barzilay, J, Heatley, GJ, Cushing, GW. Benign and malignant tumors in patients with acromegaly. Arch Intern Med 1991; 151: 1629–32.Google Scholar
  340. 340.
    Klein, I, Parveen, G, Gavaler, JS, Vanthiel, DH. Colonic polyps in patients with acromegaly. Ann Intern Med 1982; 97: 27–30.Google Scholar
  341. 341.
    Ituarte, EM, Petrini, J, Hershman, JM. Acromegaly and colon cancer. Ann Intern Med 1984; 101: 627–8.Google Scholar
  342. 342.
    Pines, A, Rozen, P, Ron, E, Gilat, T. Gastrointestinal tumors in acromegalic patients. Am J Gastroenterol 1985; 80: 266–9.Google Scholar
  343. 343.
    Ritter, MM, Richter, WO, Schwandt, P. Acromegaly and colon cancer. Ann Intern Med 1987; 106: 636–7.Google Scholar
  344. 344.
    Ziel, FH, Peters, AL. Acromegaly and gastrointestinal adenocarcinomas. Ann Intern Med 1988; 109: 514–5.Google Scholar
  345. 345.
    Brunner, JE, Johnson, CC, Zafar, S, Peterson, EL, Brunner, JF, Mellinger, RC. Colon cancer and polyps in acromegaly: increased risk associated with family history of colon cancer. Clin Endocrinol Oxf 1990; 32: 65–71.Google Scholar
  346. 346.
    Ezzat, S, Strom, C, Melmed, S. Colon polyps in acromegaly. Ann Int Med 1991; 114: 754–5.Google Scholar
  347. 347.
    Wynder, EL, Hebert, JR. Homogeneity and nutritional exposure: an impediment in cancer epidemiology? JNCI 1987; 79: 605–7.Google Scholar
  348. 348.
    Giovannucci, E. Insulin and colon cancer. Cancer Causes Control 1995; 6: 164–79.Google Scholar
  349. 349.
    McKeown-Eyssen, G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomark Prev 1994; 3: 687–95.Google Scholar
  350. 350.
    Siiteri, PK, MacDonald, PC. The role of extraglandular estrogen in human endocrinology. In: Geiger, SR, Astwood, EB, Geep, RO, eds. Handbook of Physiology. New York, NY (USA): American Physiological Society, 1973: 615–29.Google Scholar
  351. 351.
    Siiteri, PK. Obesity and peripheral estrogen synthesis. In: Frisch, RE, ed. Adipose Tissue and Reproduction. Basel, Switzerland: Karger 1990; Progr Reprod Biol Med: 14: 70–84.Google Scholar
  352. 352.
    Coulam, CB, Annegers, JF, Kranz, JS. Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol 1983; 61: 403–7.Google Scholar
  353. 353.
    Gammon, MD, Thompson, WD. Polycystic ovaries and the risk of breast cancer. Am J Epidemiol 1991; 134: 818–24.Google Scholar
  354. 354.
    Ibanez, L, Potau, N, Virdis, R, et al. Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1993; 76: 1599–603.Google Scholar
  355. 355.
    Lazar, L, Kauli, R, Bruchis, C, Nordenberg, J, Galatzer, A, Pertzelan, A. Early polycystic ovary-like syndrome in girls with central precocious puberty and exaggerated adrenal response. Eur J Endocrinol 1995; 133: 403–6.Google Scholar

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© Rapid Science Publishers 1996

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  • Rudulf Kaaks

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